Jing M, Bina S, Verma A, Hart J L, Muldoon S M
Department of Anesthesiology, Uniformed Services University of the Health Sciences (USUHS), Bethesda, Maryland 20814-4799, USA.
Anesthesiology. 1996 Aug;85(2):347-54. doi: 10.1097/00000542-199608000-00017.
Halothane and isoflurane previously were reported to attenuate endothelium-derived relaxing factor/nitric oxide-mediated vasodilation and cyclic guanosine monophosphate (cGMP) formation in isolated rat aortic rings. Carbon monoxide has many chemical and physiologic similarities to nitric oxide. This study was designed to investigate the effects of halothane and isoflurane on carbon monoxide-induced relaxations and cGMP formation in the isolated rat aorta.
Isometric tension was recorded continuously from endothelium denuded rat aortic rings suspended in Krebs-filled organ baths. Rings precontracted with submaximal concentrations of norepinephrine were exposed to cumulative concentrations of carbon monoxide (26-176 microM). This procedure was repeated three times, with anesthetics delivered 10 min before the second procedure. Carbon monoxide responses of rings contracted with the same concentration of norepinephrine (10(-6) M and 2 x 10(-6) M) used in the anesthetic-exposed preparations also were examined. The concentrations of cGMP were determined in denuded rings using radioimmunoassay. The rings were treated with carbon monoxide (176 microM, 30 s) alone, or carbon monoxide after a 10-min incubation with halothane (0.34 mM or 0.72 mM). To determine whether the sequence of anesthetic delivery influenced results, vascular rings pretreated with halothane were compared with nonpretreated rings.
Carbon monoxide (26-176 microM) caused a dose-dependent reduction of norepinephrine-induced tension, with a maximal relaxation of 1.51 +/- 0.07 g (85 +/- 7% of norepinephrine-induced contraction). Halothane (0.34 mM and 0.72 mM) significantly attenuated the carbon monoxide-induced relaxations, but only the highest concentration of isoflurane (0.53 mM) significantly attenuated the carbon monoxide-induced relaxations. Carbon monoxide (176 microM) significantly increased cGMP content (+88.1 +/- 7.1%) and preincubation of the aortic rings with halothane (0.34 mM and 0.72 mM) inhibited this increase (-70.7 +/- 6.8% and -108.1 +/- 10.6%, respectively). When aortic rings and carbon monoxide were added simultaneously to Krebs solution equilibrated with halothane (0.72 mM), no inhibition of cGMP formation occurred.
Carbon monoxide-induced endothelium-independent relaxations of rat aortic rings were decreased by clinically relevant concentrations of halothane and isoflurane. The carbon monoxide-induced elevations of cGMP were attenuated by halothane only when the anesthetic was incubated with aortic rings before carbon monoxide treatment. The possible clinical significance of the actions of the anesthetics on this endogenous vasodilator is yet to be determined.
先前有报道称，氟烷和异氟烷可减弱内皮源性舒张因子/一氧化氮介导的离体大鼠主动脉环舒张以及环磷酸鸟苷（cGMP）生成。一氧化碳在化学和生理特性上与一氧化氮有许多相似之处。本研究旨在探讨氟烷和异氟烷对一氧化碳诱导的离体大鼠主动脉舒张及cGMP生成的影响。
将去内皮的大鼠主动脉环悬挂于充满Krebs液的器官浴槽中，连续记录等长张力。用亚最大浓度的去甲肾上腺素预收缩环后，给予累积浓度的一氧化碳（26 - 176 μM）。此过程重复三次，在第二次操作前10分钟给予麻醉剂。还检测了用与麻醉暴露制剂中相同浓度的去甲肾上腺素（10⁻⁶ M和2×10⁻⁶ M）收缩的环对一氧化碳的反应。用放射免疫分析法测定去内皮环中的cGMP浓度。环单独用一氧化碳（176 μM，30秒）处理，或在与氟烷（0.34 mM或0.72 mM）孵育10分钟后用一氧化碳处理。为确定麻醉剂给药顺序是否影响结果，将用氟烷预处理的血管环与未预处理的环进行比较。
一氧化碳（26 - 176 μM）引起去甲肾上腺素诱导张力的剂量依赖性降低，最大舒张为1.51±0.07 g（去甲肾上腺素诱导收缩的85±7%）。氟烷（0.34 mM和0.72 mM）显著减弱一氧化碳诱导的舒张，但只有最高浓度的异氟烷（0.53 mM）显著减弱一氧化碳诱导的舒张。一氧化碳（176 μM）显著增加cGMP含量（+88.1±7.1%），主动脉环与氟烷（0.34 mM和0.72 mM）预孵育可抑制这种增加（分别为-70.7±6.8%和-108.1±10.6%）。当主动脉环和一氧化碳同时加入用氟烷（0.72 mM）平衡的Krebs溶液中时，未发生对cGMP生成的抑制。
临床相关浓度的氟烷和异氟烷可降低一氧化碳诱导的大鼠主动脉环非内皮依赖性舒张。仅当在一氧化碳处理前将麻醉剂与主动脉环孵育时，氟烷才会减弱一氧化碳诱导的cGMP升高。麻醉剂对这种内源性血管舒张剂作用的潜在临床意义尚待确定。
